Thymopoiesis is a highly complex process involving crosstalk interactions between developing thymocytes and their supporting stromal microenvironment. The stromal environment contains a system for ‘training’ T lineage progenitor T cells as developing thymocytes for proper binding of a T cell receptor recognizing ‘self in the context of a peptide. Progenitor T cells pass through three main developmental stages starting as ‘double-negative’ and progressing to mature functional T cells as they pass through the thymic cortex, cortico-medullary junction and medulla. Mature functional T cells are necessary for disease and cancer prevention in addition to maintaining the immunological health of an individual.
The main stromal compartments responsible for guiding developing thymocytes are lined with thymic epithelial cells (TEC). These cells are damaged by radiation exposure, chemotherapy, viral infections, certain immunosuppressant compounds in addition to age-induced atrophy. Damage to the thymic stromal cells increases the rate of atrophy that in turn reduces the functional capability of the thymus to properly train and generate T cells.
Thus, there remains a need for compositions and methods for restoring the capability of the thymus to support thymopoiesis after damage of the thymic epithelial cells (TECs).